The Massachusetts Alzheimer's Disease Research Center (ADRC) is a multi- institutional consortium composed of Harvard-affiliated facilities including the Massachusetts General Hospital, Beth Israel Hospital, McLean Hospital, Brigham & Women's Hospital, and the Harvard Division on Aging; the Massachusetts Inst of Technology; Southwestern Vermont Medical Center; and the University of Massachusetts Medical Center. Each Institution supports research in AD and has a proven track record of excellence. We have joined together in order to amplify existing research and to accelerate the pace of understanding and treating AD. The ADRC consortium provides a framework for pooling technological resources and gaining sufficient aollaborative manpower, patient enrollment, and autopsy material to conduct and wide range of studies proposed. The overall broad goals of the Massachusetts ADRC are identical to those first proposed ten years ago: To enhance currently funded research, to propose new experiments in fields of neuroscience related to dementia, and to catalyze education, training and information transfer related to AD. In order to accomplish these goals, we will retain four Core facilities that were established during the initial grant cycle. The Administrative Core is responsible for organizing and maintaining the Center. The Clinical Core examines and diagnoses patients with AD and related dementias; enrolls them into the ADRC; and refers them for participation in specific research projects. The Neuropathology Core establishes diagnoses on all brains submitted to the Tissue Resource Center; stores tissue for molecular, neurochemical, and immunocytochemical studies; and distributes brain tissue to qualified investigators. The Education and Information Transfer Core has developed programs to train the future leaders in the academic fields relevant to aging and dementia; to promote exchange of information among ADRC professionals and with the lay community; and to enroll elderly non- demented control subjects into ADRC research. The overriding mission of the ADRC is to stimulate and support research of the highest quality. This application contains five full research projects plus eight pilot projects whose broad themes center on molecular genetics, amyloid metabolism, behavioral neuroscience, and neuropathology of AD. The Core facilities provide resources for the research projects and are in turn sustained by them. Overall, the framework of the ADRC increases the involvement of Massachusetts researchers in AD and amplifies their productivity.